Maternal embryonic leucine zipper kinase in tumor cells and tumor microenvironment: An emerging player and promising therapeutic opportunity

Cancer Lett. 2023 Apr 28:560:216126. doi: 10.1016/j.canlet.2023.216126. Epub 2023 Mar 16.

Abstract

Maternal embryonic leucine zipper kinase (MELK) is a member of the AMPK (AMP-activated protein kinase) protein family, which is widely and highly expressed in multiple cancer types. Through direct and indirect interactions with other targets, it mediates various cascades of signal transduction processes and plays an important role in regulating tumor cell survival, growth, invasion and migration and other biological functions. Interestingly, MELK also plays an important role in the regulation of the tumor microenvironment, which can not only predict the responsiveness of immunotherapy, but also affect the function of immune cells to regulate tumor progression. In addition, more and more small molecule inhibitors have been developed for the target of MELK, which exert important anti-tumor effects and have achieved excellent results in a number of clinical trials. In this review, we outline the structural features, molecular biological functions, potential regulatory mechanisms and important roles of MELK in tumors and tumor microenvironment, as well as substances targeting MELK. Although many molecular mechanisms of MELK in the process of tumor regulation are still unknown, it is worth affirming that MELK is a potential tumor molecular therapeutic target, and its unique superiority and important role provide clues and confidence for subsequent basic research and scientific transformation.

Keywords: Ferroptosis; Maternal embryonic leucine zipper kinase (MELK); OTSSP167; TAM; Tumor microenvironment.

Publication types

  • Review

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation
  • Humans
  • Leucine Zippers
  • Neoplasms*
  • Protein Serine-Threonine Kinases* / metabolism
  • Tumor Microenvironment

Substances

  • Protein Serine-Threonine Kinases
  • MELK protein, human